Inferior olive serotonin and norepinephrine levels during development in the genetically dystonic rat

The dystonic (dt) rat is an autosomal recessive mutant with a motor syndrome that shares several features with idiopathic torsion dystonia in humans. In the dt rats, marked biochemical and physiological abnormalities have been localized to the olivo-cerebellar system. At the pharmacological level, the dt rats exhibit enhanced sensitivity to the behavioral effects of serotonergic (5HT) agonists, including quipazine, a drug that activates the neurons of the inferior olive (IO). High performance liquid chromatography with electrochemical detection was used to assay 5-HT, 5-hydroxyindoleacetic acid (5HIAA), and norepinephrine (NE) in micropunches of the IO in normal and dt rats at 14, 18 and 22 days of age. Samples of the rostral frontal lobes were used as internal controls. Significant age-dependent effects were seen on 5-HT and 5-HIAA levels in the IO, but not the frontal cortex, in both groups. Although both groups reached similar 5-HT levels by postnatal day 22, a significant interaction effect between age and phenotype indicated a difference in the pattern of development. Administration of quipazine (10 mg/kg, IP) to 18-day-old normal and dt rats 1 h prior to sacrifice caused significant reductions in NE, 5-HIAA and the ratio of 5-HIAA to 5-HT; however, no phenotypic differences were detected. The findings do not suggest that the differential behavioral responses to 5-HT agonists seen in normal and dt rats are the result of global abnormalities in 5-HT systems, nor do they suggest the presence of presynaptic defects in the IO.(ABSTRACT TRUNCATED AT 250 WORDS)